The implication of nanopores as versatile components in dedicated biosensors, nanoreactors, or miniaturized sequencers has considerably advanced single-molecule investigative science in a wide range of disciplines, ranging from molecular medicine and nanoscale chemistry to biophysics and ecology. Here, we employed the nanopore tweezing technique to capture amino acid-functionalized peptide nucleic acids (PNAs) with α-hemolysin-based nanopores and correlated the ensuing stochastic fluctuations of the ionic current through the nanopore with the composition and order of bases in the PNAs primary structure. We demonstrated that while the system enables the detection of distinct bases on homopolymeric PNA or triplet bases on heteropolymeric strands, it also reveals rich insights into the conformational dynamics of the entrapped PNA within the nanopore, relevant for perfecting the recognition capability of single-molecule sequencing.
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http://dx.doi.org/10.3390/polym13081210 | DOI Listing |
Nat Commun
December 2024
Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Growth differentiation factor 15, GDF15, and glucagon-like peptide-1 (GLP-1) analogues act through brainstem neurons that co-localise their receptors, GDNF-family receptor α-like (GFRAL) and GLP1R, to reduce food intake and body weight. However, their use as clinical treatments is partially hampered since both can also induce sickness-like behaviours, including aversion, that are mediated through a well-characterised pathway via the exterolateral parabrachial nucleus. Here, in mice, we describe a separate pathway downstream of GFRAL/GLP1R neurons that involves a distinct population of brain-derived neurotrophic factor (BDNF) cells in the medial nucleus of the tractus solitarius.
View Article and Find Full Text PDFEndocrinology
November 2024
Laboratory of Neurophysiology, Multidisciplinary Institute of Cell Biology [IMBICE; Argentine Research Council (CONICET); Scientific Research Commission, Province of Buenos Aires (CIC-PBA); National University of La Plata], B1906APO La Plata, Buenos Aires, Argentina.
The GH secretagogue receptor (GHSR) and the glucagon-like peptide-1 receptor (GLP-1R) are G protein-coupled receptors with critical, yet opposite, roles in regulating energy balance. Interestingly, these receptors are expressed in overlapping brain regions. However, the extent to which they target the same neurons and engage in molecular crosstalk remains unclear.
View Article and Find Full Text PDFFish Shellfish Immunol
December 2024
School of Aquatic and Life Sciences, Shanghai Ocean University, Shanghai, China. Electronic address:
Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), a scaffold protein, plays a pivotal role in the NF-κB pathway downstream of T-cell receptors (TCRs) and B-cell receptors (BCRs). As a key signaling hub, MALT1 integrates various pathways, making it essential for both innate and adaptive immunity. However, its role in the antibacterial immune responses of crustaceans remains unclear.
View Article and Find Full Text PDFNeurobiol Aging
December 2024
Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal; Centro Clínico e Académico de Coimbra, Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal; Coimbra Institute of Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Curcumin has been proposed as a potential treatment for Alzheimer's disease (AD) due to its ability to inhibit amyloid-β (Aβ) peptide aggregates and to destabilise pre-formed ones. Derivative 27 was synthesized to improve low-dose efficacy in the context of AD. Its anti-inflammatory, antioxidant and anti-amyloidogenic activities were evaluated in chemico, in vitro using AD and neuroinflammation cell models, and in vivo using the double-transgenic APP/PS1 mice.
View Article and Find Full Text PDFSci Rep
December 2024
Clinical Laboratory, Hebei General Hospital, Shijiazhuang, Hebei, China.
Objective: To explore the influence of SALL4 in cardiac fibroblasts on the progression of myocardial infarction.
Methods: Analysis of genes specifically expressed in myocardial infarction by bioinformatics methods; The impact of SALL4 on myocardial infarction was assessed using mouse ultrasound experiments and Masson staining; The effect of SALL4 on the expression levels of collagen-I and collagen-III in myocardial tissue was examined by immunohistochemical staining; The migration ability of cardiac fibroblasts was evaluated using a Transwell assay; The proliferative ability of cardiac fibroblasts was tested using a CCK-8 assay; The relative fluorescence intensity of α-SMA and CTGF in cardiac fibroblasts were checked through immunofluorescence staining experiment; The expression of SALL4, DOT1L, H3K79me2, P53, SHP2, YAP, nucleus-YAP, collagen-I, α-SMA, CTGF, and PAI-1 in myocardial tissues or cardiac fibroblasts was detected using western blot analysis.
Results: SALL4-specific high expression in myocardial infarction; SALL4 intensified the alterations in the heart structure of mice with myocardial infarction and worsened the fibrosis of myocardial infarction; SALL4 also promoted the expression of SALL4, DOT1L, H3K79me2, P53, SHP2, YAP, nucleus-YAP, collagen-I, collagen-III, α-SMA, CTGF, and PAI-1 in myocardial infarction tissues and cardiac fibroblasts; Subsequently, SALL4 could enhance the immunofluorescence intensity of α-SMA and CTGF; Moreover, SALL4 could promote the proliferation and migration of cardiac fibroblasts.
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